杜氏肌营养不良(Duchenne muscular dystrophy，DMD)是由DMD基因突变引起的抗肌萎缩蛋白缺乏的一种严重X连锁隐性遗传病，突变形式主要包括外显子缺失和重复、点突变、插入突变等，这些突变通过不同方式影响了抗肌萎缩蛋白的正常表达，最终导致疾病的发生。本研究报告了1例DMD基因第59号外显子(exon 59，E59)插入突变引起的DMD，该患儿相关生化指标明显异常，表现较为明显的DMD早期症状，并出现了多处白发。其母亲和姐姐为携带者，生化指标轻微异常，母亲有轻微临床症状，姐姐无临床症状。其他成员基因和身体状况正常。经测序和序列比对发现，该插入片段为AluYa5亚家族的Alu元件，该片段插入可产生两个终止密码子，末端含一段多聚腺苷酸尾(polyA)。为了解该插入突变对于DMD基因的影响以及与临床症状的关联，通过外显子剪接增强子(exonic splicing enhancer，ESE)预测发现，该插入并不影响E59的剪接，由此推测该插入序列会最终出现在DMD基因的mRNA序列中，插入序列中的2个终止子和polyA很可能会在翻译过程中发挥终止作用，不能产生有功能的抗肌萎缩蛋白，这可能是导致DMD发生的机制。另外该患儿除了典型的DMD症状外，还出现了过早白发症状。本研究首次报道了1例DMD基因编码区插入Alu元件导致的DMD，为研究Alu序列逆转座引发基因突变提供线索，同时扩展了对DMD基因突变的认识。

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.